rs141323589

Variant names:

• chr14-53152646-C-T
• rs141323589
• NM_001160148.2:c.453G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001160148.2(DDHD1):​c.453G>A​(p.Pro151Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00351 in 1,613,068 control chromosomes in the GnomAD database, including 251 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0065 (41 hom., cov: 32)
  • Exomes 𝑓: 0.0032 (210 hom.)
• Consequence: DDHD1 NM_001160148.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -1.15
• Publications: 2 publications found

Genes affected

DDHD1 (HGNC:19714): (DDHD domain containing 1) This gene is a member of the intracellular phospholipase A1 gene family. The protein encoded by this gene preferentially hydrolyzes phosphatidic acid. It is a cytosolic protein with some mitochondrial localization, and is thought to be involved in the regulation of mitochondrial dynamics. Overexpression of this gene causes fragmentation of the tubular structures in mitochondria, while depletion of the gene results in mitochondrial tubule elongation. Deletion of this gene in male mice caused fertility defects, resulting from disruption in the organization of the mitochondria during spermiogenesis. In humans, mutations in this gene have been associated with hereditary spastic paraplegia (HSP), also known as Strumpell-Lorrain disease, or, familial spastic paraparesis (FSP). This inherited disorder is characterized by progressive weakness and spasticity of the legs. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Aug 2015]

DDHD1-DT (HGNC:55441): (DDHD1 divergent transcript)

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP6: Variant 14-53152646-C-T is Benign according to our data. Variant chr14-53152646-C-T is described in ClinVar as Benign. ClinVar VariationId is 380446.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.15 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0529 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001160148.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDHD1	NM_001160148.2	MANE Select	c.453G>A	p.Pro151Pro	synonymous	Exon 1 of 13	NP_001153620.1	Q8NEL9-1
	DDHD1	NM_001160147.2		c.453G>A	p.Pro151Pro	synonymous	Exon 1 of 13	NP_001153619.1	Q8NEL9-4
	DDHD1	NM_030637.3		c.453G>A	p.Pro151Pro	synonymous	Exon 1 of 12	NP_085140.2	Q8NEL9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDHD1	ENST00000673822.2	MANE Select	c.453G>A	p.Pro151Pro	synonymous	Exon 1 of 13	ENSP00000500986.2	Q8NEL9-1
	DDHD1	ENST00000357758.3	TSL:1	c.453G>A	p.Pro151Pro	synonymous	Exon 1 of 12	ENSP00000350401.3	Q8NEL9-2
	DDHD1	ENST00000907176.1		c.453G>A	p.Pro151Pro	synonymous	Exon 1 of 15	ENSP00000577235.1

Frequencies

GnomAD3 genomes AF: 0.00647 AC: 984 AN: 152190 Hom.: 41 Cov.: 32

Gnomad AFR AF: 0.00159

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0558

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00503

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.00860

GnomAD2 exomes AF: 0.0144 AC: 3553 AN: 247212 AF XY: 0.0105

Gnomad AFR exome AF: 0.00115

Gnomad AMR exome AF: 0.0970

Gnomad ASJ exome AF: 0.00161

Gnomad EAS exome AF: 0.00584

Gnomad FIN exome AF: 0.0000466

Gnomad NFE exome AF: 0.0000631

Gnomad OTH exome AF: 0.0105

GnomAD4 exome AF: 0.00320 AC: 4673 AN: 1460760 Hom.: 210 Cov.: 31 AF XY: 0.00268 AC XY: 1944 AN XY: 726726

African (AFR) AF: 0.000836 AC: 28 AN: 33474

American (AMR) AF: 0.0938 AC: 4193 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.00130 AC: 34 AN: 26120

East Asian (EAS) AF: 0.00386 AC: 153 AN: 39686

South Asian (SAS) AF: 0.000128 AC: 11 AN: 86248

European-Finnish (FIN) AF: 0.0000190 AC: 1 AN: 52596

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.0000459 AC: 51 AN: 1111850

Other (OTH) AF: 0.00333 AC: 201 AN: 60320

GnomAD4 genome AF: 0.00648 AC: 987 AN: 152308 Hom.: 41 Cov.: 32 AF XY: 0.00708 AC XY: 527 AN XY: 74462

African (AFR) AF: 0.00159 AC: 66 AN: 41578

American (AMR) AF: 0.0560 AC: 856 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00173 AC: 6 AN: 3468

East Asian (EAS) AF: 0.00504 AC: 26 AN: 5156

South Asian (SAS) AF: 0.000621 AC: 3 AN: 4830

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000162 AC: 11 AN: 68036

Other (OTH) AF: 0.00851 AC: 18 AN: 2116

Alfa AF: 0.00190 Hom.: 1

Bravo AF: 0.0122

Asia WGS AF: 0.00375 AC: 13 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.000237

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not specified (2)
-	-	1	Hereditary spastic paraplegia (1)
-	-	1	Hereditary spastic paraplegia 28 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	4.9
DANN	Benign	0.95
PhyloP100		-1.2
PromoterAI		0.045	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs141323589; hg19: chr14-53619364;